Safety/Efficacy of Induction Agents With Tacrolimus, MMF, and Rapid Steroid Withdrawal in Renal Transplant Recipients (INTAC)

This study has been completed.
Sponsor:
Information provided by:
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00113269
First received: June 7, 2005
Last updated: August 9, 2011
Last verified: August 2011
  Purpose

The purpose of this study is to compare the safety and efficacy of different induction agents (alemtuzumab, basiliximab or rabbit anti-thymocyte globulin) in renal transplant recipients treated with tacrolimus, mycophenolate mofetil (MMF) and a rapid steroid withdrawal.


Condition Intervention Phase
Kidney Transplantation
Drug: basiliximab
Drug: rabbit anti-thymocyte globulin
Drug: tacrolimus
Drug: alemtuzumab
Drug: mycophenolate mofetil
Drug: steroids
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 4, Randomized, Open-label, Comparative, Multicenter Study to Assess the Safety and Efficacy of Induction Agents, Alemtuzumab, Basiliximab or Rabbit Anti-thymocyte Globulin in Combination With Tacrolimus, MMF, and a Rapid Steroid Withdrawal in Renal Transplant Recipients

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Patient Incidence of Biopsy-confirmed Acute Rejection (BCAR) at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    A BCAR is a suspected new rejection w/in 6 mos. of skin closure, confirmed by Banff Grade ≥1A assigned by a pathologist. The Banff 97 classification system is used for interpreting histology of allograft biopsies, including Mild (1A/1B), Moderate (2A/2B) & Severe (3).

    Kaplan Meier analysis was used to estimate % of pts. w/event. Patients w/no event at time of scheduled visit or whose 1st event was after premature discontinuation of study drug/tacrolimus were censored on the scheduled day of a) assessment, b) of premature treatment discontinuation or c) last evaluation, whichever came 1st.



Secondary Outcome Measures:
  • Overall Patient Incidence of BCAR [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

    Overall patient incidence of BCAR is defined as a suspected new rejection at any time following skin closure confirmed by a Banff Grade ≥ 1A as assigned by a local pathologist. Incidence is reported as the percentage of patients with BCAR. The Banff 97 scale is a classification system for interpreting histology of allograft biopsies. The grades range from Mild (1A & 1B) to Moderate (2A & 2B) to Severe (3).

    End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.


  • Efficacy Failure [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

    Efficacy Failure is a composite measure of biopsy confirmed acute rejection, graft loss and death. Data is reported as the percentage of patients with Efficacy Failure.

    End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.


  • Clinically Treated Acute Rejection [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

    Clinically treated acute rejection is defined as patient incidence of any rejection (suspected or otherwise) for which treatment was provided. Data is reported as the percentage of patients with Clinically Treated Acute Rejection.

    End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.


  • Time to First BCAR [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

    Time to first BCAR is defined as the number of days from skin closure to the first episode of BCAR.

    End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.


  • Graft Survival at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    Graft survival is defined as no graft loss (re-transplant, return to dialysis for more than 30 days or death) with 12 months of skin closure.

    Kaplan Meier analysis was used to estimate percentage of patients with event. Patients with no event by the time of the scheduled visit or whose first event was after premature discontinuation of randomized study drug or tacrolimus were censored on the scheduled day of assessment, on the day of premature treatment discontinuation or last evaluation day, whichever came first.


  • Overall Graft Survival [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

    Overall graft survival is defined as not having graft loss (re-transplant, return to dialysis for more than 30 consecutive days, or death) at any time following skin closure. Data is reported as the percentage of patients with Overall Graft Survival.

    End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.


  • Patient Survival at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    Patient survival is defined as not dead within 12 months after skin closure.

    Kaplan Meier analysis was used to estimate percentage of patients with event. Patients with no event by the time of the scheduled visit or whose first event was after premature discontinuation of randomized study drug or tacrolimus were censored on the scheduled day of assessment, on the day of premature treatment discontinuation or last evaluation day, whichever came first.


  • Overall Patient Survival [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

    Overall patient survival is defined as not dead at any time following skin closure. Data is reported as the percentage of patients with Overall Patient Survival.

    End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.


  • Renal Function Abnormalities Based on Creatinine Clearance [ Time Frame: 1 month and End of Study (36 months) ] [ Designated as safety issue: No ]

    Increases in creatinine clearance usually indicates an improvement.

    Change in creatinine clearance from month 1 was calculated.

    Change from 1 month is calculated by month 36 - month 1.


  • Renal Function Abnormalities Based on Serum Creatinine [ Time Frame: 1 month and End of Study (36 months) ] [ Designated as safety issue: No ]

    Decrease in serum creatinine usually indicates an improvement.

    Change in creatinine clearance from month 1 was calculated.

    Change from 1 month is calculated by month 36 - month 1.



Enrollment: 501
Study Start Date: May 2005
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alemtuzumab High-Risk Patients
Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
Drug: tacrolimus
oral
Other Name: Prograf, FK506
Drug: alemtuzumab
Intravenous (IV)
Other Name: campath
Drug: mycophenolate mofetil
oral
Other Names:
  • MMF
  • CellCept
Drug: steroids
IV and/or oral
Active Comparator: Conventional High-Risk Patients
Rabbit anti-thymocyte globulin, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
Drug: rabbit anti-thymocyte globulin
IV
Other Name: Thymoglobulin
Drug: tacrolimus
oral
Other Name: Prograf, FK506
Drug: mycophenolate mofetil
oral
Other Names:
  • MMF
  • CellCept
Drug: steroids
IV and/or oral
Experimental: Alemtuzumab Low- Risk Patients
Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody < 20% and first transplant and non-African American
Drug: tacrolimus
oral
Other Name: Prograf, FK506
Drug: alemtuzumab
Intravenous (IV)
Other Name: campath
Drug: mycophenolate mofetil
oral
Other Names:
  • MMF
  • CellCept
Drug: steroids
IV and/or oral
Active Comparator: Conventional Low-Risk Patients
Basiliximab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody < 20% and first transplant and non-African American
Drug: basiliximab
IV
Other Name: simulect
Drug: tacrolimus
oral
Other Name: Prograf, FK506
Drug: mycophenolate mofetil
oral
Other Names:
  • MMF
  • CellCept
Drug: steroids
IV and/or oral

Detailed Description:

A 2 arm (1 Active, 1 Active Control) study is to compare the safety and efficacy of different induction agents (alemtuzumab, basiliximab or rabbit anti-thymocyte globulin) in renal transplant recipients treated with tacrolimus, MMF and a rapid steroid withdrawal.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recipient of a primary or re-transplanted deceased donor kidney or a primary or re-transplanted non-human leukocyte antigen (HLA) living donor kidney (ie., HLA identical or 0 antigen mismatch deceased donor kidneys are allowed).

Exclusion Criteria:

  • Patient has previously received an organ transplant other than a kidney
  • Patient receiving chronic steroid therapy at time of transplant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00113269

  Show 29 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Central Contact Astellas Pharma Global Development
  More Information

Additional Information:
Publications:
Hanaway M.J. , M.D.; Woodle E.S., M.D.; Mulgaonkar S., M.D.; et al. Alemtuzumab Induction in Renal Transplantation. N Engl J Med May 2011;364:1909-19

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Clinical Trial Registries, Astellas Pharma Global Development
ClinicalTrials.gov Identifier: NCT00113269     History of Changes
Other Study ID Numbers: 20-04-003
Study First Received: June 7, 2005
Results First Received: June 7, 2011
Last Updated: August 9, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Astellas Pharma Inc:
Treatment Effectiveness
Treatment Efficacy
Anti-rejection therapy
Immunosuppression
Therapy, antirejection
Renal Transplantation
Transplantation, Kidney
Transplantation, Renal
Grafting, Kidney

Additional relevant MeSH terms:
Tacrolimus
Mycophenolate mofetil
Antilymphocyte Serum
Basiliximab
Mycophenolic Acid
Alemtuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014